Abstract
ABSTRACTCoordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect. The kinase domains of AurkB and AurkC were responsible for their different ability to phosphorylate Histone H3 Serine 10 (H3S10P) and regulate metaphase timing. Using an Oct4-photoactivatable GFP fusion protein (Oct4-paGFP) and fluorescence decay after photoactivation assay, we found that AurkB overexpression reduced Oct4 retention in the nucleus. Finally, we show that blastomeres with higher AurkC level elevated pluripotency gene expression, which were inclined to enter the inner cell mass lineage and subsequently contributed to the embryo proper. Collectively, our results are the first demonstration that the activity of mitotic kinases can influence cell fate decisions in mammalian preimplantation embryos and have important implications to assisted reproduction.
Highlights
Precise and timely segregation of sister chromatids during cell division is essential for early embryo development
We found that increasing Aurora kinase C (AurkC) level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis
By using mRNA overexpression, siRNA knockingdown and live imaging, we show that the speed of mitosis and the degradation rate of securin in mouse preimplantation embryos can be controlled by the level of Aurora kinase B (AurkB) and AurkC
Summary
Precise and timely segregation of sister chromatids during cell division is essential for early embryo development. A significant number of AurkC−/− embryos showed division defect which results in subfertility, while AurkB seemed not required in cleavage stage embryos but become important in blastocysts (Fernandez-Miranda et al, 2011; Schindler et al, 2012) In human, both AurkB and AurkC are expressed in preimplantation embryos, and AurkC level remained high until 8-cell stage (Avo Santos et al, 2011). Demonstrated that difference in the activity of cell division kinases has significant impact on cell fate decision
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